Download Adherence in the new era of HAART A call for community

Adherence in the new era of
HAART
A call for community pharmacists
Blake Max, PharmD
University of Illinois at Chicago
Ruth Rothstein CORE Center
Cook County Bureau of Health Services
Points to Ponder
• “Adherence is the key mediator between
medical practice and patient outcomes”
• “Drugs don’t work in patients who don’t
take them”
-C.Everett Koop MD
Objectives
• Identify predictors of virologic success
• Recognize the relationship between adherence and
successful outcomes in the new era of HAART
• Assess treatment strategies to help achieve HIV
treatment goals
• Recognize medication adherence barriers and develop a
plan to overcome such barriers.
• Discuss case studies identified in a community
pharmacy to help improve medication adherence
Scope of the Problem
• Four fundamental facts:
1. Medication adherence is poor for most chronic diseases.
- 40-80% of pts from clinical trials for of for a chronic condition
Most dramatic
after first 6 months of therapy (eg. statins)
2. Many interventions have been tested to improve medication
adherence, but a unifying recommendation for “best practice” is
still missing.
3. No consensus on what constitutes adequate adherence (70%, 80%,90%?)
4. 33-69% of all medication-related hospitalizations are due to poor
medication adherence.
Predictors of Virologic Success
•
•
•
•
•
potency of ART regimen (the new HAART era)
Excellent adherence
Low baseline viremia
baseline CD4 count
Rapid in VL ( > 1 log drop in 4-12 weeks)
Patient Factors and Adherence
• Most important are psycho-social situations
- Younger age
- Substance use
- Perceived stress
- Depression
- Lack if knowledge/literacy
All have shown to be important factors associated
with adherence
Adherence and ART
(The new era)
• Viral suppression, rates of resistance, improved survival are
correlated with high rates of ART adherence.
• Treatment must be maintained for a lifetime.
• Adherence to HIV meds has been well studied, however
interventions to improve ART adherence need further research.
• Less than 100% adherence may not apply in the new HAART era.
- Improved potency
- Simplified regimens
• Adherence is addressed in the DHHS treatment guidelines “as the
cornerstone for effective HAART regimens”
What do we Know Now About
Adherence to ART?
• How much adherence is enough?
– Original estimation was > 95%, but it may be
a bit less
– Recent data by Bangsberg et al, show that
adherence rates of around 70% may actually
be sufficient for NNRTI- and boosted PI-based
regimens.
Bangsberg DR et al, Clinical Infectious Diseases 2006; 43:939-41.
Bangsberg DR, et al. IAS 2007, Abstract WEPEB111
Adherence to unboosted PI and virologic failure
90
80
Patients with virologic failure, %
70
60
50
VF%
3-D Column 2
3-D Column 3
40
30
20
10
0
>95%
80-90%
70-80%
<70%
Adherence, % MEMS Caps
Ritonavir boosted PI and Adherence
n=53 (Kaletra)
Adherence measured using MEMS
Mean adherence = 73%
Adherence
Rates
>95%
9094.9%
8089.9%
7079.9%
5069.9%
<50%
% pts with
VL<400(n)
at 24
weeks
70% (10)
88% (8)
100% (9)
100% (4)
55% (11)
73% (11)
Conclusions:
- Moderate levels of adherence can lead to virologic suppression in most pts on Kaletra.
- These data challenge belief that near-perfect adherence is necessary to achieve
virologic suppression in the current HAART era.
-Shuter et al. JAIDS 45(1) 2007
Boosted PIs More Forgiving of
Suboptimal Adherence
•
Increased risk of virologic breakthrough with < 95% adherence to antiviral
regimen (multivariate analysis)
– Unboosted PI (n = 752): 66% increased risk
– NNRTI (n = 631): 47% increased risk
– RTV-boosted PI (n = 251): not significant
Variable Associated
With Virologic
Breakthrough
Adjusted Hazard Ratios (95% CI)
Single PI
NNRTI
Boosted PI
Adherence < 95%
1.66 (1.38-2.01)
1.47 (1.01-2.14)
1.05 (0.46-2.42)
IDU history
1.37 (1.15-1.63)
1.47 (1.08-2.02)
1.69 (0.86-3.34)
Viral load
1.06 (0.89-1.26)
1.12 (0.83-1.51)
0.63 (0.33-1.11)
CD4+ cell count
0.93 (0.89-0.96)
0.88 (0.81-1.51)
0.98 (0.6-1.27)
Gross R, et al. CROI 2006. Abstract 533.
NNRTI More Forgiving of Suboptimal
Adherence Than Unboosted PI
• 109 indigent patients in San Francisco
– 56 unboosted PI, 53 NNRTI regimen
• VL < 400 reliably seen with NNRTI if adherence > 54%, but with
unboosted PI, only with very high adherence
VL < 400 copies/mL (%)
100
PI
NNRTI
100
80
80
60
60
40
40
20
20
0
0
0-53
54-73
74-93 94-100
Adherence (Pill Count) (%)
Bangsberg DR, et al. CROI 2005. Abstract 616.
0-53
54-73
74-93 94-100
Adherence (Electronic Measurement) (%)
GS 903E: Percent of Patients With VL
< 50 c/mL Through 5 Years
192 wks
144 wks
Study 903E
(open label)
Study 903
TDF + 3TC + EFV
TDF + 3TC + EFV (n = 86) ≈ (Atripla)
d4T + 3TC + EFV
Patients With VL
< 50 c/mL (%)
100
ld
g/
m
83%
80
60
40mL
M = F (N = 86)
20
0
0
1
2
3
Years
Cassetti I, et al. International Congress on Drug Therapy in HIV Infection
Glasgow, Scotland 2006. Poster P152.
4
5
Strategies to achieve Treatment Goals
• Regimen selection- tailored to the pt
- A regimen tailored to the pt allows for better
adherence.
• Tailoring regimen includes:
- Expected side effects
- Convenience
- Comorbidities
- Drug interactions and other concomitant meds
- Pretreatment genotype
Regimen Attributes With Impact on
Adherence: Patient Perceptions
Total pills per day: 14%
Dosing frequency: 13%
Adverse events: 12%
Attributes related to
Pill burden
Adverse events
Dosing restrictions
Prescriptions
Diet restrictions: 11%
Pill size: 10%
Number of refills: 9%
Number of copays: 9%
Number of prescriptions: 8%
Number of bottles: 8%
Bedtime dosing: 6%
0%
5%
10%
15%
Stone VE, et al. J Acquir Immune Defic Syndr. 2004;36:808-816.
20%
25%
Why Do Patients Miss Doses?
Reasons Given for Missing Antiretroviral Doses (Structured Questionnaire), %
0
Too busy/simply forgot
Away from home
Change in daily routine
Felt depressed/overwhelmed
Took drug holiday/medication break
Ran out of medication
Too many pills
Worried about becoming “immune”
Felt drug was too toxic
Wanted to avoid adverse effects
Did not want others to notice
Reminder of HIV infection
Confused about dosage direction
Did not think it was improving health
To make it last longer
Was told the medicine is no good
10
20
30
40
50
60
52
46
45
27
20
20
19
19
18
17
17
16
14
13
10
9
Gifford AL, et al. J Acquire Immune Defic Syndr. 2000;23:386-395.
Possible interventions:
Simplify dosing schedule
Decrease pill burden
Other
What Do We Know Now About
Regimen Predictors of Adherence ?
• What are the characteristics ARV
regimens that are associated with better
adherence?
– Less complex regimens
– Regimens with fewer side effects. Side effects
are the most common reason patients
discontinue their ARV regimens.
• What is the evidence?
Toxicity Is a Major Reason for
Discontinuation of First-Line HAART
• ICONA Study Group
– Median follow-up:
45 weeks
– Study population:
862 ARV-naive patients
– 84.3% receiving
unboosted PI + NRTIs
– Discontinuations:
n = 312 (36%)
d’Arminio Monforte A, et al. AIDS. 2000;14:499-507.
Cause of discontinuation
Toxicity
Nonadherence
Failure
Other
8%
20%
58%
14%
PASPORT: Study Objectives
• Evaluate relative impact of regimen
characteristics on patient adherence
– Different HAART regimen characteristics (i.e., dosing
frequency)
– Strata within each regimen characteristic (i.e. BID,
QD all at once, QD different times, mixed QD/BID)
Stone VE, et al. JAIDS. 2004;36:808-816.
PASPORT: Impact of Regimen
Characteristics on Adherence
6.06%
7.61%
13.74%
8.17%
13.02%
8.77%
12.67%
8.98%
9.64%
Stone VE, et al. JAIDS. 2004;36:808-816.
11.34%
Total pills per day
Dosing frequency
Diet restrictions
Adverse effects
Pill Size
No. of refills
No. of copays
No. of prescriptions
No. of bottles
Bedtime dosing?
PASPORT: Conclusions
• Many regimen characteristics contribute to adherence,
but pills per day, dosing frequency, diet restrictions, and
side effects contribute more than others
• Once daily ‘QD’ regimens only provide an adherence
benefit over other HAART regimens if they can be taken
all at 1 time, contain few pills and no dietary restrictions.
• Underscores the adherence benefit of new compact
regimens using co-formulated pills.
Stone VE, et al. JAIDS 2004;36:808-16.
Goals of Therapy for TreatmentExperienced Patients
• “In those with prior treatment and drug resistance, the
goal is to resuppress HIV RNA levels maximally and
prevent further selection of resistance mutations, if
possible.” – US DHHS Guidelines, October 10, 2006[1]
• “Trials with newer antiretroviral agents have shown that
it is possible to achieve plasma HIV-1 RNA levels below
50 copies/mL even in highly treatment–experienced
patients.” – IAS-USA Guidelines, August 2006[2]
1. DHHS. Available at: http://aidsinfo.nih.gov. Accessed August 27, 2007.
2. Hammer SM, et al. JAMA. 2006;296:827-843.
Role for the Community Pharmacist
• Ensure that the regimen fits the patients lifestyle.
- Can you simplify?
• Recognizing drug interactions with ART
• Adherence counseling/assessment at each
encounter.
- Early detection of poor adherence and prompt
intervention can greatly reduce the chance of virologic
failure and development of viral resistance.
Barriers to Adherence
• What can the Pharmacist do?
- Educate pt about the regimen, the disease, and its tx
Too busy? Use medication handouts
Internet resources: www.aidsinfonet.org
www.aidsmeds.com
www.hivpositive.com
- Reinforce pt knowledge of pharmacy resources and
provide adequate access
- Ensure correct Rx and that meds are taken as directed
- Assess for simplification
- Be aware of potential drug-drug interactions
Access to Pharmaceutical Care
(Health-System Barriers)
• Factors to consider include:
- Pharmacists knowledge of therapeutic agents and
strategies used to treat HIV infection.
- Assistance in processing 3rd party payment for meds
and/or access to drug-assistance programs (ADAP)
- Pharmacy schedules that include PM or weekend
hours for counseling pts or other obligations that
prevent daytime visits.
- Delivery services for ART medications
- Offering adherence tool devices (pill boxes)
Summary
• HAART regimens, including regimens for tx-experienced
pts have become increasingly convenient over the last
few years.
- Pts prefer compact regimens
- Better adherence on compact regimens
• Community pharmacist are a valuable resource:
- Medication education
- Recommendations for treatment of side effects
- Refill records
- Monitor drug-drug interactions